Molecular Imaging of the biomarker phosphatidylserine (PS) in vivo is important for diagnosis of diseases and assessment of efficacy of therapy. Effective PS-recognising agents are annexin A5 and its variants. Technetium-labeled annexin A5 can be injected into a subject and, subsequently, Single Photon Emission Tomography (SPECT) can be applied to assess the biomarker PS. In order to assess the biomarker PS sensitively and specifically, it is mandatory that the complex between technetium and annexin A5 is stable in vivo and is rapidly cleared from the blood circulation.
Current complexes of technetium and annexin A5 are based on chemical bonding of Tc (technetium) to a non-specific site of the annexin molecule. For example, JP2006-316004 discloses a compound obtained by bonding 4′-aminomethyl-N,N′-trimethylene-dibenzohydroxamide to annexin V through a linker, which compound is capable of complexing technetium. WO 98/48699 discloses a complex in which Tc99m is linked to the annexin via succinimidyl hydrazinonicotinate (HYNIC). Such complexes suffer from insufficient stability. Moreover, it is not possible to direct the label at a specific site of the annexins, especially a site which does not interfere with its affinity profile. Jung et al., J. Nucl. Med. 2008 49 (Supplement 1):304P, refers to a 1-124 labeled recombinant annexin molecule for apoptosis imaging using small animal PET (positron emission tomography).